Neuroscience Letters 655 (2017) 137–142 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Short communication The glutamate receptor antagonists CNQX and MPEP decrease fast ripple events in rats treated with kainic acid Laura Medina-Ceja ∗ , Carla García-Barba Laboratory of Neurophysiology, Department of Cellular and Molecular Biology, CUCBA, University of Guadalajara, Jalisco, Mexico h i g h l i g h t s • The AMPA/KA receptor antagonist CNQX decreases occurrence of fast ripples. • The mGluR5 receptor antagonist MPEP decreases fast ripple events. • There was no effect on fast ripple duration, amplitude or frequency from CNQX/MPEP. • There is an important contribution of glutamate receptors in fast ripple generation. a r t i c l e i n f o Article history: Received 18 April 2017 Received in revised form 6 June 2017 Accepted 29 June 2017 Available online 30 June 2017 Keywords: CNQX Fast ripples Hippocampus Kainic acid MPEP Status epilepticus a b s t r a c t Fast ripples (FR) are high frequency oscillations (250–600 Hz) that have been associated with epilepsy. FR are assumed to be generated in small areas of the hippocampus (1 mm 3 ) that contain pathologically interconnected glutamate pyramidal cell clusters. Additionally, a relation between glutamate neu- rotransmission and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainite (AMPA/KA) and metabotropic mGluR5 receptors is well established. Therefore, we hypothesized that antagonism of these glutamate receptors would decrease FR activity. For this propose, we induced status epilepticus with a kainic acid injection in the posterior right hippocampus and performed intracranial EEG recordings to detect and evaluate the presence of FR 15 days after the injection. The glutamate AMPA/KA receptor antagonist CNQX (10 mg/kg) and the mGluR5 antagonist MPEP (20 mg/kg) were administered intraperi- toneally, and the effects of the drugs were evaluated for a period of three hours after their administration. The results show a decrease in the number of FR in the first hour after drug administration in both cases (CNQX, p = 0.0125; MPEP, p = 0.0132) and a return to basal values in the third hour of the experiment, but not significant differences in the number of oscillations per event of FR, and the frequency and duration of each event of FR. We therefore conclude that blockade of AMPA/KA and mGluR5 receptors transiently decreases the generation of FR; however, the mechanisms by which this effect is achieved are to be further analyzed in future experiments. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Fast ripples (FR) are high frequency oscillations (HFOs) ranging from 250 to 600 Hz, and they have been regarded as a potential marker of epileptogenicity in temporal and extratemporal seizures for over a decade [1–12]. This activity was initially detected in human and animal epileptic hippocampal tissue and in animals that ∗ Corresponding author at: Laboratorio de Neurofisiología, Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Camino Ing. R. Padilla Sánchez 2100, Las Agujas, Nextipac, Zapopan, Jalisco, CP 45110, Mexico. E-mail address: lauramedcej@gmail.com (L. Medina-Ceja). develop seizures during the latency period [1–3]. There is also evi- dence that HFOs can be detected in non-epileptic neocortex [13]. Nevertheless, the majority of studies report higher rates of HFOs in epileptic tissue and better surgical outcome when areas containing FR are resected; further supporting our opening remarks [14–18]. There are several hypotheses regarding the genesis of FR, includ- ing hypersynchronous bursts of action potentials from pyramidal cells (Dhzala and Staley), initiation from gap junctions [4], and asynchronous activity of individual or clusters of non-event-related pyramidal neurons [19,20]. Recently, a theory resulting from a com- putational model proposed that the aforementioned mechanisms can all be involved in the generation of FR under different cir- cumstances, the key elements being hyperactive pyramidal cells, desynchronization and local field potentials dominated by action http://dx.doi.org/10.1016/j.neulet.2017.06.056 0304-3940/© 2017 Elsevier B.V. All rights reserved.